Research Paper Volume 11, Issue 13 pp 4367—4381
Age-related changes in B cell metabolism
- 1 The Wistar Institute, Philadelphia, PA 19104, USA
- 2 Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
- 3 Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27705, USA
Received: February 21, 2019 Accepted: June 24, 2019 Published: July 8, 2019
https://doi.org/10.18632/aging.102058How to Cite
Copyright: Kurupati et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Antibody responses to vaccinations or infections decline upon aging. In this study we tested if metabolic changes in B cells may contribute to attenuation of responses to influenza vaccination in aged humans. Our data show that aging affects mitochondrial functions in B cells leading to increases in mitochondrial reactive oxygen species (MROS) and mitochondrial mass (MM) in some aged B cell subsets and decreases in expression levels of Sirtuin 1 (SIRT1), Forkhead box protein (FOX)O1 and carnitine palmitoyltransferase 1 (CPT-1). Seahorse analyses showed minor defects in glycolysis in the aged B cells after activation but a strong reduction in oxidative phosphorylation. The analyses of the transcriptome revealed further pronounced defects in one-carbon metabolism, a pathway that is essential for amino acid and nucleotide metabolism. Overall our data support the notion that the declining ability of aged B cells to increase their metabolism following activation contributes to the weakened antibody responses of the elderly.
Abbreviations
ACC1: Acetyl-CoA carbocylase; ASC: antibody secreting cells; CROS: cellular reactive oxygen species; CPT-1: carnitine palmitoyltransferase 1; ECAR: extracellular acidification rates; FCCP: carbonyl cyanide-4-phenylhydrazone; FAO: fatty acid beta-oxidation; FOX: Forkhead box protein; Glc: glucose; MM: mitochondria mass; MMP: mitochondrial membrane potential; MROS: mitochondrial reactive oxygen species; ODN: oligonucleotide; OM: oligomycin; pAKT: phosphorylated protein kinase B; SLC: solute carrier family; SIRT1: Sirtuin 1; TCA: tricarboxylic acid; TIV: trivalent inactivated influenza vaccine; VNA: virus neutralizing antibodies.